Two Novel Functional Mutations in Promoter Region of SCN3B Gene Associated with Atrial Fibrillation

Lin, Liyan; Li, Ke; Tian, Beijia; Jia, Mengru; Wang, Qianyan; Xu, Chengqi; Xiong, Liang; Wang, Qing; Zeng, Yali; Wang, Pengyun

doi:10.3390/life12111794

Open AccessArticle

Two Novel Functional Mutations in Promoter Region of SCN3B Gene Associated with Atrial Fibrillation

by

Liyan Lin

^1,†,

Ke Li

^2,3,†,

Beijia Tian

^2,3,

Mengru Jia

^2,3,

Qianyan Wang

⁴,

Chengqi Xu

^2,3,

Liang Xiong

¹,

Qing Wang

^2,3,

Yali Zeng

^1,* and

Pengyun Wang

^1,*

¹

Department of Clinical Laboratory, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430077, China

²

Key Laboratory of Molecular Biophysics of the Ministry of Education, Cardio-X Institute, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China

³

Human Genome Research Center, College of Life and Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China

⁴

Liyuan Cardiovascular Center, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430077, China

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Life 2022, 12(11), 1794; https://doi.org/10.3390/life12111794

Submission received: 28 September 2022 / Revised: 1 November 2022 / Accepted: 3 November 2022 / Published: 5 November 2022

(This article belongs to the Special Issue The Molecular Mechanism of Cardiovascular Disease)

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Abstract

The sodium voltage-gated channel beta subunit 3 (SCN3B) plays a crucial role in electrically excitable cells and conduction tissue in the heart. Some previous studies have established that genetic modification in sodium voltage-channel genes encoding for the cardiac β-subunits, such as SCN1B, SCN2B, SCN3B and SCN4B, can result in atrial fibrillation (AF). In the current study, we identified two rare variants in 5′UTR (NM_018400.4: c.-324C>A, rs976125894 and NM_018400.4: c.-303C>T, rs1284768362) of SCN3B in two unrelated lone AF patients. Our further functional studies discovered that one of them, the A allele of c.-324C>A (rs976125894), can improve transcriptional activity and may raise SCN3B expression levels. The A allele of c.-324C>A (rs976125894) has higher transcriptional activity when it interacts with GATA4, as we confirmed transcription factor GATA4 is a regulator of SCN3B. To the best of our knowledge, the current study is the first to demonstrate that the gain-of-function mutation of SCN3B can produce AF and the first to link a mutation occurring in the non-coding 5′UTR region of SCN3B to lone AF. The work also offers empirical proof that GATA4 is a critical regulator of SCN3B gene regulation. Our findings may serve as an encyclopedia for AF susceptibility variants and can also provide insight into the investigation of the functional mechanisms behind AF variants discovered by genetic methods.

Keywords: atrial fibrillation; mutation; SCN3B; GATA4

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MDPI and ACS Style

Lin, L.; Li, K.; Tian, B.; Jia, M.; Wang, Q.; Xu, C.; Xiong, L.; Wang, Q.; Zeng, Y.; Wang, P. Two Novel Functional Mutations in Promoter Region of SCN3B Gene Associated with Atrial Fibrillation. Life 2022, 12, 1794. https://doi.org/10.3390/life12111794

AMA Style

Lin L, Li K, Tian B, Jia M, Wang Q, Xu C, Xiong L, Wang Q, Zeng Y, Wang P. Two Novel Functional Mutations in Promoter Region of SCN3B Gene Associated with Atrial Fibrillation. Life. 2022; 12(11):1794. https://doi.org/10.3390/life12111794

Chicago/Turabian Style

Lin, Liyan, Ke Li, Beijia Tian, Mengru Jia, Qianyan Wang, Chengqi Xu, Liang Xiong, Qing Wang, Yali Zeng, and Pengyun Wang. 2022. "Two Novel Functional Mutations in Promoter Region of SCN3B Gene Associated with Atrial Fibrillation" Life 12, no. 11: 1794. https://doi.org/10.3390/life12111794

APA Style

Lin, L., Li, K., Tian, B., Jia, M., Wang, Q., Xu, C., Xiong, L., Wang, Q., Zeng, Y., & Wang, P. (2022). Two Novel Functional Mutations in Promoter Region of SCN3B Gene Associated with Atrial Fibrillation. Life, 12(11), 1794. https://doi.org/10.3390/life12111794

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Two Novel Functional Mutations in Promoter Region of SCN3B Gene Associated with Atrial Fibrillation

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